Intro Flashcards
What heart related issues can occur?
Malformed
Block Blood supply
Rupture
Cardiac Failure
Rhythm disturbance leading to failed cardiac output
Why is cardiac energy essential?
Heart beats 100,000/day
Pumps 10 metric tons of blood/day
Requires more energy than any other organ
Cycles through 16kg of ATP/day (20-30X its own weight)
Energy produced in mitochondria
Mitochondria are 30% of myocardial cell volume
What impacts the effectiveness of cardiac energy?
Energy reserves can ensure only 20secs of normal activity
Energy produced by oxidative phosphorylation
At maximum exercise uses 90% of its capacity
What are some heart diseases/disorders?
Ischaemic Heart Disease Congenital Heart Disease Disorders of Cardiac Muscle Disorders of Cardiac Rhythm Disorders of the Vascular System
The heart mainly produces (energy) ATP through oxidative pathways.
What are these?
- Glucose Oxidation:
- Provides 10 - 40% of energy
- More oxygen efficient
- ATP/02=3
- Glucose converted to pyruvate to acetyl coa and then energy (ATP)
Efficient use of oxygen however results in less storage therefore other pathways such as fatty acid are oxidation considered
- Fatty Acid B-oxidation:
Provides 60-90% of energy
Requires more 02 than glucose
ATP/02=2.6
If a heart transplant is pursued, why are the nerves not needed to be tied?
Heart does not require innovation
Cardiac muscle is similar to striated muscle except the intercalated discs that form cardiac muscle into a syncytium differs from parallel fibres seen in skeletal muscle.
True or false
True
Cardiac muscle similar to skeletal muscle rather than smooth muscle, particularly in concern to genes, however diseases differ. Although there may be some overlap such as Duchenne muscular dystrophy whereby cardiac involvement may also occur and this suggests that for dystrophin there is not much difference between skeletal and cardiac muscle.
True or false
True
The heart is composed of which 3 major types of cardiac muscle?
- Atrial
- Ventricular
- Specialised excitatory and conductive muscle fibres
Which forms of cardiac muscle contract in much the similar way as skeletal muscle except that the duration of contraction is much longer?
Atrial and ventricular types
Which forms of cardiac muscle contract only feebly?
Excitatory and conductive fibres
Cardiac muscle fibers are made up of what and are parallel to what?
individual cells connected in series and in parallel to one another
How are cardiac muscle fibers arranged?
In a latticework, with the fibers dividing, recombining and then spreading again
How is cardiac muscle similar to skeletal muscle
Cardiac muscle is started in the same manner as in skeletal muscle
Cardiac muscle have myofibrils that contain actin and myosin filaments almost identical to those found in skeletal muscle.
These filaments lie side by side and slide along one another during contraction in the same manner as occurs in skeletal muscle
What is the main difference between cardiac muscle and skeletal muscle?
Cardiac muscle do not tire with contractions
What is an example of a gene that is important in cardiomyopathies that begin with skeletal forms expressed, however later cardiac forms play a more important role?
Genes such as troponin
What composes the intercalated disc and is also important for transmission of messages?
Desmosomes
Transverse tubules and thin and thick filaments essential for coordination of contraction and adequate functioning of heart and are all controlled by what?
Set of genes
What is released within T tubules and what does the excite?
Calcium. Excites further calcium to be released from sarcoplasmic reticulum to bring about contraction
What genes play a role in arrhythmias?
Many calcium genes that play a role in arrhythmias such as CPVT which is due to mutations in RYR2 gene, this gene is important for transferring calcium back into sarcoplasmic reticulum
Also calmodulin genes play role -n heart arrhythmia when mutated
Cardiac cells are so interconnected that..
when one of these cells becomes excited, the action potential spreads to all of them, from cell to cell throughout the latticework interconections
- Cardiac muscle is composed of how many syncytium and what do they constitute?
- What does this allow for?
- 2
The atrial syncytium: Constitutes the walls of two atria
The ventricular syncytium: Constitutes the walls of the two ventricles
- The atria to contract a short time ahead of ventricular contraction
Overlap of genes between heart conditions creates difficulty to..
For now focus in clinics is placed upon what?
What can be used in the future? What is the advantage of this? What is the disadvantage?
- Know which genes should be tested
- Panel testing for arrhythmias and cardiomyopathies
- WES and WGS with advantage that all info is there thus ability to look back when you know more if you don’t find mutants in currently known genes. Disadvantage is might not enable good coverage of well known genes compared to panels
How is circulation different for foetus?
Low oxygen tensions because fed through placenta which has lost half its oxygen to maternal circulation
Describe fetal circulation
Two sets of arteries- umbilical and pulmometry
Placenta accepts unoxygenated blood through from the foetus through blood vessels that leave the foetus through the umbilical cord. When blood enters placenta it is oxygenated. The oxygen rich blood then returns to the fetus via the third vessel in the umbilical cord (umbilical vein). The oxygen rich blood that enters the fetus passes through the fetal liver and enters the right atrium. Ductus venosus which plays important role to lower pressure as blood goes into right side of heart.
The hole between the top two heart chambers (right and left atrium) is called apatent foramen ovale(PFO). This hole allows the oxygen rich blood to transfer from right atrium to left atrium and then to the left ventricle and out the aorta. As a result the blood with the most oxygen gets to the brain.
How can babies survive with low intrauterine oxygen tension?
- Adequate O2 tension
- Different form of haemoglobin: Foetal haemoglobin
- ↓ foetal O2 Consumption
- 0 thermoregulation
- Reduced physiological functions compared to adults e.g do not need to shiver or utilise muscles - Differential blood flow
- Liver directly from Umbilical Vein
- Brain & Heart - high degree of O2 saturation – differential velocities of incoming venous blood streams directing oxygenated blood through the foramen ovale
- Low fetal O2 saturation maintains architecture of the fetal circulation by causing pulmonary vascular constriction
Why is foetal circulation very important?
Many issues are initiated antenatally such as maternal diabetes is the most common cause of hypertrophic cardiomyopathy in the Newborn infant
In cardiac conduction pathways what is the pacemaker?
Sinus atrial node
Number of genes during development of early disorders are well understood
True or false
False
Non well understood
In cardiac conduction pathways where does the signal travel through?
AV node and once there, there is delay before travels through into ventricle
Describe cardiac conduction
An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node). The atria are then activated. The electrical stimulus travels down through the conduction pathways and causes the heart’s ventricles to contract and pump out blood. The 2 upper chambers of the heart (atria) are stimulated first and contract for a short period of time before the 2 lower chambers of the heart (ventricles).
The electrical impulse travels from the sinus node to the atrioventricular node (also called AV node). There, impulses are slowed down for a very short period, then continue down the conduction pathway via the bundle of His into the ventricles. The bundle of His divides into right and left pathways, called bundle branches, to stimulate the right and left ventricles.
What is the most common arrhythmia in adults and professional sports players have a much higher incidence of this later in life
Atrial fibrillation
What are forms of Atrial Dysrhythmias?
Atrial Tachycardias- Supra-ventricular Tachycardia (SVT)
Atrial Fibrillation
Problems at atrioventricular mode can lead to what?
Heart block
What is observed in atrioventricular node disease?
Problems at atrioventricular node can lead to heart block
Can bypass the AV node through accessory pathways
Proportion of Wolfe Parkinson white cases have genetic cause although most of time this isn’t problem
Bundle branch blocks may occur but do not seem to be major problem and underlying causes are unknown
True or false
True
Describe mitochondrial genetics?
Mitochondria contain their own DNA
Multiple mitochondria/cell
Multiple copies of mitochondrial DNA/ mitochondria
Maybe different mitochondrial DNA mutations in different mitochondria
- Heteroplasmy/homoplasmy
- Most proteins within the mitochondria coded for by nuclear genes
Different proportions of abnormal mitochondria may exist and in some cases can have excess which will then drive individual over threshold for disease
True or false
True
Importantly the nuclear genome provides key genes or the genes for key components of mitochondria as well as the mitochondrial genome, thus coordination needed between both genomes
True or false
True
What sort of Genes can effect Cardiac Function?
- Developmental Genes - tend to cause congenital heart disease
- House keeping Genes
- Structural Protein - cardiomyopathies
- Ion channels- arrhythmias
- Energy Production
- Molecular Switches
Why does 1 phenotype not equate to 1 genotype?
There are also environmental influences which can push patient over threshold for disease or protection
